Damage to and diseases of the central nervous system (CNS) often result in loss of motor and sensory functions, which are frequently irreversible, in body parts below the level of the lesion. Over one and one-half million people are suffering from some form of paralysis in the United States. The development of treatment procedures to decrease the severity of CNS damage and to promote regeneration and return of function awaits the elucidation of the variables that control such processes. This research project proposes investigations of changes that occur in the neuronal systems in the proximal and distal portions of the spinal cord after spinal cord injury. Neurochemical, neuro-physiological and neuropathological data indicate that a synaptic reorganization may occur in the distal segment and be responsible for the development of spasticity. Neuroanatomical peculiarities have also been observed in the area above such lesions. This reorganization could prevent return of function even though regeneration may take place. This research project proposes investigations of the neurochemical and neuroanatomical changes that take place during spinal shock and the development of spinal spasticity. The information will be used to investigate treatment procedures to alleviate these debilitating conditions by modulating intact segmental and previously damaged descending neuronal systems. Methods to prevent, reverse or modulate the neuronal changes that occur will also be investigated. These studies should hopefully produce new insights into the processes that must be understood to make CNS functional regeneration possible.